K JAYASINGHE1,2,3, Z STARK4,8, P KERR1,2, C QUINLAN3,7, A MALLETT6,8, RENAL GENETICS FLAGSHIPS, KIDGEN COLLABORATIVE8,9
1Monash Health, Clayton, Australia, 2Monash University, Clayton, Australia, 3Murdoch Children’s Research Institute, Clayton, Australia, 4Victorian Clinical Genetics Services, , Clayton, Australia, 5Melbourne Genomics Health Alliance, Melbourne, Australia, 6Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia, 7Department of Paediatric Nephrology, Royal Children’s Hospital, Parkville, Australia, 8Australian Genomics Health Alliance, , Australia, 9Melbourne Genomics Health Alliance, , Australia
Aim: To describe diagnostic outcomes of clinically accredited genomic testing delivered by nationwide multidisciplinary team (MDT) clinics for patients with suspected genetic kidney disease (GKD).
Background: With increased understanding of GKD, genomic testing is translating from research to clinic. Rigorous evaluation of clinical practice and patient outcomes is required to guide value-based healthcare.
Methods: Sequential incident patients undergoing clinically indicated genomic testing for presumed GKD from 18 Australian MDT clinics 2016-19 were analyzed (HREC/16/MH/251). A molecular diagnosis constituted clinical reporting of pathogenic and/or likely pathogenic variant/s in gene/s associated with the patient’s kidney phenotype with concordant inheritance. All genomic testing included restriction of variant analysis to a phenotype-derived gene list.
Results: Results:1088 patients underwent genomic testing between 2016-2019. 48% of the cohort were male, median age at the time of genomic test was 30 years (range <1year to 81). The most common sequencing approach was targeted exome (n=477), exome sequencing (n=220) and whole genome sequencing (n=148). 491 patients (45%) received a positive diagnostic on genomic sequencing. Of these, 71/448(16%) had reclassification of their original diagnosis, 176/448(39%) had clarification of their diagnosis, and 187/448(42%) had confirmation of the suspected diagnosis following genomic testing. In addition, 14/448 (3%) patients with a previous unknown cause of renal failure received a diagnosis. The diagnostic yield was highest in infants<1 year of age (68%) and lowest (37%) in those aged above 50 (OR 3.6, 95%CI 19.1-6.72, p<0.001, for infants compared to age>50 at time of test).
Conclusions: In this nationwide, pragmatic pediatric and adult cohort, genetic testing demonstrated substantial diagnostic utility, especially in children and young adults. Clinical utility studies are required to clarify impact of these diagnostic outcomes.
Dr Kushani Jayasinghe is an adult nephrologist based at Monash Health with an interest in genetic kidney disease. Her PhD studies through Monash University focuses on the clinical utility and feasibility of genomic sequencing in patients with suspected genetic kidney disease.